The overall goal of this application is to provide the candidate, a senior investigator with an extensive background in dental materials research, with experience in the techniques used to study the regeneration of living dental tissues, pulp and dentin, as a result of injury or insult from dental disease and their subsequent interactions with dental materials. Advances in regenerative medicine are paving the way for a new era in restorative dentistry and this training will position the candidate to be a key player in contributing to this field. This experience, including the specific research project, are in support of the goals of the NIDCR which is to encourage research on the repair and regeneration of orofacial tissues, to determine the safety of commonly used dental materials, and to provide an adequate and well-trained research workforce. To accomplish the overall goal, a series of experiments have been designed by the candidate, with the advice of the sponsor, Dr. Tony Smith (U. Birmingham), an expert in this field. Dentin adhesives and glass ionomer restoratives, with and without a bioactive glass additive, will serve as the test materials. The research plan for this senior fellowship application has three specific aims. The first aim is to treat human dentin with acid of systematically greater strength (lower pH), representing differences in current "selfetching" dental adhesives, as well as commercial versions of self-etching adhesives and conventional glass ionomer, and to identify and quantitate the bioactive molecules, such as growth factors, that are released. The second aim is to use cell culture and gene expression to examine the viability of the bioactive molecules released from dentin by the various materials in terms of their ability to stimulate dentin regeneration. The third aim is to use the tooth slice organ culture model developed at the University of Birmingham to study the extent of cell death and the healing process of dentin exposed to specific dental materials;and to determine if the healing process can be enhanced by incorporating into the self-etching adhesive and glass ionomer a calcium and phosphate releasing material, a silica-based bioactive glass, that is currently being studied by the applicant for use in dental adhesives and restoratives. Public Health Relevance: This work is relevant to public health in that it investigates the manner in which tooth tissues respond to materials used to restore teeth and repair and regenerate themselves. This work also seeks to identify dental materials that may aid in the healing process by releasing the tooth's own molecules needed for the repair or regeneration process.